Role of Vγ9Vδ2+ γδ T cells in juvenile idiopathic arthritis

Introduction

T cells (TC) bearing Vγ9Vδ2+ γδ TC receptor (TCR), are a subset of innate CD4-CD8- TC pro-inflammatory and immunoregulatory TC recognizing non-peptidic phosphorylated mediator isopentenyl pyrophosphate (IPP) in the mevalonate pathway. The role Vγ9Vδ2+ TC has never been explored in JIA joints.

Patients and methods

Mononuclear cells (MC) isolated from synovial fluids (SF) of 47 patients with monoarticular (M, n = 11), pauciarticular (P, n = 19), extended (E, n = 5), polyarticular (Po, n = 2), systemic (S, n = 4), psoriatic (Ps, n = 4), enthesitis related (Sp, n = 2) JIA were dually stained with monoclonal antibodies to CD3 and variable (V) regions of the γδ TCR. Flow cytometry of fresh SFMC and following in vitro 10 days stimulation with 0.5 mg/ml IPP plus 100 IU/ml interleukin-2 (IL-2) was performed.

Results

Vγ9Vδ2+TC constituted 6.8 ± 1.3%, 6.4 ± 0.9%, 4.6 ± 1.0%, 3.8 ± 3.6%, 5.6 ± 1.6%, 6.1 ± 0.1% and 1.3 ± 0.8% of the SF CD3+cells in the M, P, E, Po, Ps, Sp and S JIA types respectively, and were significantly higher in ANA+ (n = 19) than ANA- (n = 22) patients (7.8 ± 0.9% vs 4.1 ± 0.6% p < 0.004, Student T test). IPP and IL-2 activated SFMC showed a greater expansion of Vγ9Vδ2+ TC of ANA+ (n = 12) than ANA- (n = 18) patients (61.2 ± 17.1% vs 31.7 ± 7.6%, p < 0.005) and of patients with M or P (n = 11) relative to S, E or Po (n = 6) JIA (44.9 ± 10.9 vs 16.2 ± 10.5 p < 0.02).

Conclusion

SF Vγ9Vδ2+ TC responses are stronger in M and P than in E, Po, and S JIA and in ANA+ than – patients, suggesting that a potent Vγ9Vδ2+ TC response may augment acute inflammation while limiting progression to chronic and destructive arthritis.